Effect of rolipram on muscarinic acetylcholine receptor binding in the intact mouse brain

The effect of rolipram, a selective inhibitor of phosphodiesterase type 4 (PDE(4)) and elevating cyclic AMP (cAMP), on in vivo and in vitro (3)H-N-methylpiperidyl benzilate ((3)H-NMPB) binding to muscarinic acetylcholine receptors in the mouse brain was examined. Rolipram significantly decreased in vivo (3)H-NMPB binding in the cerebral cortex, hippocampus and striatum, whereas in vitro (3)H-NMPB binding in these regions was not altered. Saturation experiments on in vivo binding in conjunction with the kinetic analysis revealed that the apparent association rate constant (k(on)) of (3)H-NMPB binding in vivo was significantly decreased by rolipram. A similar decrease in the apparent association rate constant (k(on)) by rolipram was reported for dopamine D(1) and D(2) receptor binding in vivo. These results indicate that rolipram plays an important role in the global modulation of apparent rates of ligand-receptor interactions in the intact brain.